Prevalence of Intracranial Aneurysms in Patients with Infrarenal Abdominal Aortic Aneurysms: A Multicenter Experience.

Prior studies suggest high prevalence of intracranial aneurysms (IA) in patients with infrarenal abdominal aortic aneurysms (AAA). We reviewed our multicenter experience in clinical detection/treatment of IAs in AAA patients and estimated the risk of IA in patients with AAA relative to patients without AAA. We reviewed cases of vascular surgery infrarenal AAA repairs at three Mayo Clinic sites from January 1998 to December 2018. Concurrent controls were randomly matched in a 1:1 ratio by age, sex, smoking history, and head imaging characteristics. Conditional logistic regression was used to calculate odds ratios. We reviewed 2,300 infrarenal AAA repairs. Mean size of AAA at repair was 56.9 ± 11.4 mm; mean age at repair, 75.8 ± 8.0 years. 87.5% of the cases ( n = 2014) were men. Head imaging was available in 421 patients. Thirty-seven patients were found to have 45 IAs for a prevalence of 8.8%. Mean size of IA was 4.6 ± 3.5 mm; mean age at IA detection, 72.0 ± 10.8 years. Thirty (81%) out of 37 patients were men. Six patients underwent treatment for IA: four for ruptured IAs and two for unruptured IAs. All were diagnosed before AAA repair. Treatment included five clippings and one coil-assisted stenting. Time from IA diagnosis to AAA repair was 16.4 ± 11.0 years. Two of these patients presented with ruptured AAA, one with successful repair and a second one that resulted in death. Odds of IA were higher for patients with AAA versus those without AAA (8.8% [37/421] vs. 3.1% [13/421]; OR 3.18; 95% confidence interval, 1.62-6.27, p < 0.001). Co-prevalence of IA among patients with AAA was 8.8% and is more than three times the rate seen in patients without AAA. All IAs were diagnosed prior to AAA repair. Surveillance for AAA after IA treatment could have prevented two AAA ruptures and one death.

Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

ANTECEDENTES: La efectividad de la endarterectomía carotídea (carotid endarterectomy, CEA) en la prevención de un accidente cerebrovascular depende de que este procedimiento tenga pocos riesgos. El objetivo de este estudio fue evaluar la frecuencia y el momento de aparición de las complicaciones tras una CEA, lo que podría clarificar los mecanismos subyacentes y ayudar a establecer una política de altas hospitalarias segura. MÉTODOS: Se utilizaron los datos de los pacientes incluidos en cuatro grandes ensayos de intervención carotídea (VACS, ACAS, ACST-1 y GALA; 1983-2007). Para el presente análisis se utilizaron los datos de pacientes sometidos a CEA por estenosis de la arteria carótida asintomática recogidos inmediatamente tras la aleatorización. Se consideraron diferentes intervalos entre el procedimiento, la muerte o el accidente cerebrovascular: intraoperatorio día 0, postoperatorio día 0, postoperatorio días 1-3 y postoperatorio días 4-30. RESULTADOS: En el análisis se incluyeron 3.694 pacientes. Se detectaron complicaciones graves relacionadas con el procedimiento en 103 (2,8%) pacientes (18 accidentes cerebrovasculares fatales, 68 accidentes cerebrovasculares no fatales, 11 infartos de miocardio fatales y 6 muertes por otras causas). De los 86 accidentes cerebrovasculares, 67 (78%) fueron ipsilaterales, 17 (20%) contralaterales y dos (2%) vertebrobasilares. Los accidentes cerebrovasculares fueron isquémicos en 45 (52%) casos, hemorrágicos en 9 (10%) y no se pudo determinar el subtipo de ictus en 32 (37%). La mitad de los accidentes cerebrovasculares ocurrieron el día de la CEA. De todas las complicaciones graves registradas, 44 (43%) ocurrieron en el día 0 (20 intraoperatorias, 17 postoperatorias y 7 en períodos poco definidos), 23 (22%) entre los días 1-3 y 36 (35%) entre los días 4-30. CONCLUSIÓN: En este estudio, al menos la mitad de los accidentes cerebrovasculares relacionados con la CEA fueron isquémicos e ipsilaterales respecto a la arteria tratada. La mitad de todas las complicaciones de la CEA ocurrieron el día de la cirugía, pero un tercio de los casos se presentaron después del día 3, cuando muchos pacientes ya habían sido dados de alta.

Prevalence of Previously Undiagnosed Abdominal Aortic Aneurysms in Patients with Intracranial Aneurysms: From the Brain and Aortic Aneurysms Study (BAAS).

BACKGROUND: A relationship between intracranial and abdominal aortic aneurysms (AAA) has been appreciated through genome-wide association studies suggesting a shared pathophysiology. However, the actual prevalence of AAA in patients presenting with ruptured intracranial aneurysms is not known. Our aim was to estimate the prevalence of previously undiagnosed AAA in patients presenting with aneurysmal subarachnoid hemorrhage (aSAH) to see if it may be high enough to justify formally testing the utility of screening. METHODS: A prospective, observational inception cohort study of 81 consecutive patients presenting to Mayo Clinic Florida with aSAH was performed from August 14, 2011 to February 10, 2014. These individuals were then screened using an abdominal ultrasound technique for an AAA. Our primary end point was detection of AAA. Our secondary end points were 30-day good-to-fair functional status (modified Rankin scale < 4) and all-cause mortality. RESULTS: We detected an AAA in 10 patients (rate: 12%; 95% CI 6-22%) with aSAH. The mean diameter of these AAA was 3.4 ± 1.0 cm. Among these 10 patients, there was one death within the first month of aSAH hospitalization. There were no significant differences in demographic or clinical characteristics based on AAA detection status. Mean follow-up time was 4.7 years. The rate of good-to-fair functional status at 30-days was 79%. All-cause mortality during follow-up at 1-year was higher for patients with AAA (36%; 95% CI 0-61%) compared to patients without AAA (7%; 95% CI 1-14%) (log-rank p = 0.045). CONCLUSIONS: The co-prevalence of AAA in patients presenting with ruptured brain aneurysms may be sufficiently high such that screening for AAA among likely survivors of aSAH might be appropriate. Larger studies would be needed to establish a net clinical benefit from screening AAA and then treating newly identified large AAAs in this morbid population.

Ischaemic stroke.

There are about 25.7 million stroke survivors worldwide. Ischaemic stroke remains the most common type of stroke. Numerous modifiable risk factors have been identified, including behaviors such as cigarette smoking and sedentary lifestyle and treatable medical comorbidities such as hypertension, hyperlipidemia and atrial fibrillation. Once considered irreversible, acute ischaemic stroke is now amenable to acute medical and endovascular therapies to reduce infarct volume. Many advances are expected in the years to come, particularly in the areas of prevention and recovery.

Genetic variants associated with myocardial infarction in the PSMA6 gene and Chr9p21 are also associated with ischaemic stroke.

BACKGROUND: Ischaemic stroke shares common traditional risk factors with coronary artery disease (CAD) and myocardial infarction (MI). This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans. METHODS: Included in the study were a Caucasian series (713 ischaemic stroke patients, 708 controls) and a small African American series (166 ischaemic stroke patients, 117 controls). Twenty single-nucleotide polymorphisms (SNPs) previously shown to be associated with CAD or MI were genotyped and assessed for association with ischaemic stroke and ischaemic stroke subtypes using odds ratios (ORs) from multivariable logistic regression models. RESULTS: In Caucasians, four SNPs on chromosome 9p21 were significantly associated with risk of cardioembolic stroke, the strongest of which was rs1333040 (OR 1.55, P = 0.0007); similar but weaker trends were observed for small vessel stroke, with no associations observed regarding large vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome 14q13 was associated with overall ischaemic stroke in both Caucasians (OR 0.80, P = 0.036) and African Americans (OR 0.31, P = 0.020). CONCLUSIONS: Our results provide evidence that chromosome 9p21 variants are associated with cardioembolic ischaemic stroke in Caucasians and with overall ischaemic stroke in African Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to ischaemic stroke in both populations. These findings require validation, particularly the preliminary findings regarding African Americans given the small size of that series.

White matter hyperintensity volume is increased in small vessel stroke subtypes.

OBJECTIVE: White matter hyperintensity (WMH) may be a marker of an underlying cerebral microangiopathy. Therefore, we hypothesized that WMH would be most severe in patients with lacunar stroke and intracerebral hemorrhage (ICH), 2 types of stroke in which cerebral small vessel (SV) changes are pathophysiologically relevant. METHODS: We determined WMH volume (WMHV) in cohorts of prospectively ascertained patients with acute ischemic stroke (AIS) (Massachusetts General Hospital [MGH], n = 628, and the Ischemic Stroke Genetics Study [ISGS], n = 263) and ICH (MGH, n = 122). RESULTS: Median WMHV was 7.5 cm³ (interquartile range 3.4-14.7 cm³) in the MGH AIS cohort (mean age 65 ± 15 years). MGH patients with larger WMHV were more likely to have lacunar stroke compared with cardioembolic (odds ratio [OR] = 1.87 per SD normally transformed WMHV), large artery (OR = 2.25), undetermined (OR = 1.87), or other (OR = 1.85) stroke subtypes (p < 0.03). These associations were replicated in the ISGS cohort (p = 0.03). In a separate analysis, greater WMHV was seen in ICH compared with lacunar stroke (OR = 1.2, p < 0.02) and in ICH compared with all ischemic stroke subtypes combined (OR = 1.34, p < 0.007). CONCLUSIONS: Greater WMH burden was associated with SV stroke compared with other ischemic stroke subtypes and, even more strongly, with ICH. These data, from 2 independent samples, support the model that increasing WMHV is a marker of more severe cerebral SV disease and provide further evidence for links between the biology of WMH and SV stroke.

Design of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST).

RATIONALE: Carotid endarterectomy (CEA) and medical therapy were shown superior to medical therapy alone for symptomatic (> or =50%) and asymptomatic (> or =60%) stenosis. Carotid angioplasty stenting (CAS) offers a less invasive alternative. Establishing safety, efficacy, and durability of CAS requires rigorous comparison with CEA in symptomatic and asymptomatic patients. AIMS: The objective is to compare the efficacy of CAS versus CEA in patients with symptomatic (> or =50%) or asymptomatic (> or =60%) extracranial carotid stenosis. DESIGN: The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) is a prospective, randomized, parallel, two-arm, multi-center trial with blinded endpoint adjudication. Primary endpoints are analyzed using standard time-to-event statistical modeling with adjustment for major baseline covariates. Primary analysis is on an intent-to-treat basis. STUDY OUTCOMES: The primary outcome is the occurrence of any stroke, myocardial infarction, or death during a 30-day peri-procedural period, and ipsilateral stroke during follow-up of up to four years. Secondary outcomes include restenosis and health-related quality of life.

Prestroke physical activity and early functional status after stroke.

BACKGROUND: The importance of physical activity as a modifiable risk factor for stroke in particular and cardiovascular disease in general is well documented. The effect of exercise on stroke severity and stroke outcomes is less clear. This study aimed to assess that effect. METHODS: Data collected for patients enrolled in the Ischemic Stroke Genetics Study were reviewed for prestroke self-reported levels of activity and four measures of stroke outcome assessed at enrollment and approximately 3 months after enrollment. Logistic regression was used to assess the association between physical activity and stroke outcomes, unadjusted and adjusted for patient characteristics. RESULTS: A total of 673 patients were enrolled; 50.5% reported aerobic physical activity less than once a week, 28.5% reported aerobic physical activity one to three times weekly, and 21% reported aerobic physical activity four times a week or more. Patients with moderate and high levels of physical activity were more likely to have higher Barthel Index (BI) scores at enrollment. A similar association was detected for exercise and good outcomes for the Oxford Handicap Scale (OHS). After 3 months of follow-up, moderate activity was still associated with a high BI score. No significant association was detected for activity and the OHS or Glasgow Outcome Scale at follow-up after adjustment for patient characteristics. CONCLUSIONS: Higher levels of self-reported prestroke physical activity may be associated with functional advantages after stroke. Our findings should be seen as exploratory, requiring confirmation, ideally in a longitudinal study of exercise in an older population.

Lack of aggregation of ischemic stroke subtypes within affected sibling pairs.

OBJECTIVE: To establish whether subtypes of ischemic stroke aggregate within ischemic stroke-affected sibling pairs more than expected by chance alone. METHODS: This retrospective family study was based on a pooled analysis of two cohorts of male and female adult sibling pairs with symptomatic ischemic stroke. One hospital-based cohort of 404 individuals (first proband seen August 30, 1999) was recruited from the United States and Canada, and another population-based cohort of 198 individuals (first proband seen April 17, 1997) was recruited from Umeå, Sweden. Subtype diagnoses were based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Agreement for subtype diagnoses within families was poor (mean +/- asymptotic SE kappa = 0.17 +/- 0.04). Occurrence of one ischemic stroke subtype in a proband was not associated with a greater likelihood of that subtype being the qualifying stroke subtype in the sibling. Comparable levels of agreement were seen when restricting the analysis to same-sex sibling pairs (kappa = 0.22 +/- 0.05) to sibling pairs in which the proband's stroke occurred before the age of 65 years (kappa = 0.16 +/- 0.05) or to pairs in which the proband's stroke occurred at or after the age of 65 years (kappa = 0.19 +/- 0.05). CONCLUSIONS: The subtype of ischemic stroke in a proband was a poor determinant of the subtype of ischemic stroke in the respective sibling. This suggests that many genetic risk factors for ischemic stroke may not be specific for one subtype.

Family history of stroke and severity of neurologic deficit after stroke.

BACKGROUND: A family history of stroke is an independent risk factor for stroke. OBJECTIVE: To assess whether severity of neurologic deficit after stroke is associated with a family history of stroke. METHODS: The Ischemic Stroke Genetics Study, a five-center study of first-ever symptomatic ischemic stroke, assessed case subjects prospectively for a family history of stroke-affected first-degree relatives. Certified adjudicators used the NIH Stroke Scale (NIHSS) to determine the severity of neurologic deficit. RESULTS: A total of 505 case subjects were enrolled (median age, 65 years; 55% male), with 81% enrolled within 1 week of onset of symptoms. A sibling history of stroke was associated with more severe stroke. The odds of an NIHSS score of 5 or higher were 2.0 times greater for cases with a sibling history of stroke compared with cases with no sibling history (95% CI, 1.0 to 3.9). An association of family history of stroke in parents or children with stroke severity was not detected. CONCLUSIONS: A sibling history of stroke increased the likelihood of a more severe stroke in the case subjects, independent of age, sex, and other potential confounding factors. Other family history characteristics were not associated with stroke severity.

Correlation of proband and sibling stroke latency: the SWISS Study.

The authors found a correlation between the age at which probands experience an incident stroke and the age at which their siblings experience an incident stroke (r = 0.68; p < 0.0001). Proband-sibling incident stroke latency correlations were observed in analyses restricted to siblings concordant for smoking (r = 0.68; p < 0.0001), diabetes (r = 0.73; p < 0.0001), and hypertension (r = 0.63; p < 0.0001). In the authors' cohort of affected sibling pairs, inherited factors were important determinants of incident ischemic stroke latency.

The impact of privacy protections on recruitment in a multicenter stroke genetics study.

The authors reviewed the recruitment of stroke-affected sibling pairs using a letter-based, proband-initiated contact strategy. The authors randomly sampled 99 proband enrollment forms (Phase 1) and randomly sampled 50 sibling reply cards (Phase 2). The sibling response rate was 30.6%, for a pedigree response rate of 58%. Of the siblings who replied, 96% authorized further contact. Median time from proband enrollment to pedigree DNA banking, which required 3+ probands, was 134 days.

Use of Ephedra-containing products and risk for hemorrhagic stroke.

This case-control study examined the association between Ephedra use and risk for hemorrhagic stroke. For use of Ephedra at any dose during the 3 days before the stroke, the adjusted OR was 1.00 (95% CI 0.32 to 3.11). For daily doses of < or =32 mg/day, the OR was 0.13 (95% CI 0.01 to 1.54), and for >32 mg/day, the OR was 3.59 (95% CI 0.70 to 18.35). Ephedra is not associated with increased risk for hemorrhagic stroke, except possibly at higher doses.

Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial.

BACKGROUND: Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both. METHOD: To analyze the relationship between admission glucose level and clinical outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure. RESULTS: There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased (p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA. CONCLUSIONS: In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.

Lack of clinical significance of early ischemic changes on computed tomography in acute stroke.

CONTEXT: The prevalence and clinical significance of early ischemic changes (EICs) on baseline computed tomography (CT) scan of the head obtained within 3 hours of ischemic stroke are not established. OBJECTIVE: To determine the frequency and significance of EIC on baseline head CT scans in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA (recombinant tissue plasminogen activator) Stroke Trial. DESIGN AND SETTING: The original study, a randomized controlled trial, took place from January 1991 through October 1994 at 43 sites, during which CT images were obtained within 3 hours of symptom onset and prior to the initiation of rt-PA or placebo. For the current analysis, detailed reevaluation was undertaken after October 1994 of all baseline head CT scans with clinical data available pretreatment (blinded to treatment arm). PATIENTS: Of 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%). MAIN OUTCOME MEASURES: Frequency of EICs on baseline CT scans; association of EIC with other baseline variables; effect of EICs on deterioration at 24 hours (>/=4 points increase from the baseline National Institutes of Health Stroke Scale [NIHSS] score); clinical outcome (measured by 4 clinical scales) at 3 months, CT lesion volume at 3 months, death at 90 days; and symptomatic intracranial hemorrhage (ICH) within 36 hours of treatment. RESULTS: The prevalence of EIC on baseline CT in the combined rt-PA and placebo groups was 31% (n = 194). The EIC was significantly associated with baseline NIHSS score (rho = 0.23; P<.001) and time from stroke onset to baseline CT scan (rho = 0.11; P =.007). After adjusting for baseline variables, there was no EIC x treatment interaction detected for any clinical outcome, including deterioration at 24 hours, 4 clinical scales, lesion volume, and death at 90 days (P>/=.25), implying that EIC is unlikely to affect response to rt-PA treatment. After adjusting for NIHSS score (an independent predictor of ICH), no EIC association with symptomatic ICH at 36 hours was detected in the group treated with rt-PA (P>/=.22). CONCLUSIONS: Our analysis suggests that EICs are prevalent within 3 hours of stroke onset and correlate with stroke severity. However, EICs are not independently associated with increased risk of adverse outcome after rt-PA treatment. Patients treated with rt-PA did better whether or not they had EICs, suggesting that EICs on CT scan are not critical to the decision to treat otherwise eligible patients with rt-PA within 3 hours of stroke onset.

Thrombolysis in patients with transient neurologic deficits.

What is the risk of thrombolysis in patients with acute stroke who might recover without treatment? In the National Institute of Neurological Disorders and Stroke rt-PA for Acute Stroke Trial, 2.6% of patients taking placebo showed spontaneous 24-hour recovery, compared to 11.5% of recombinant tissue-type plasminogen activator (rt-PA)-treated patients (p < 0.001). There were no symptomatic ICH in the patients taking placebo; one hypertensive, rt-PA-treated patient hemorrhaged. Assuming the National Institute of Neurological Disorders and Stroke protocol is followed rigorously, patients with acute stroke rarely recover spontaneously and the thrombolytic risk is low.

Feasibility of an affected sibling pair study in ischemic stroke: results of a 2-center family history registry.

BACKGROUND AND PURPOSE: We sought to determine pedigree availability for a concordant sibling pair study of genetic risk factors in ischemic stroke. METHODS: Probands with confirmed ischemic stroke were prospectively enrolled. Family histories were obtained by systematic interview. A study neurologist prospectively assigned stroke subtype. RESULTS: Of 310 probands (median age, 75 years; range, 26 to 97 years; 48% women), 75% had at least 1 living sibling; 10%, at least 1 concordant living sibling; 2%, at least 1 concordant sibling living in the same city; and 7%, at least 1 concordant living and 1 discordant living sibling. Likelihood of having a concordant sibling increased significantly with proband age, even after adjustment for sibship size (P=0.002). Positive family history of stroke was not related to either proband stroke subtype or risk factor profile. CONCLUSIONS: Approximately 10 probands were screened to find 1 potentially concordant living sibling. A concordant sibling pair study should be multicentered and enable enrollment of siblings from diverse geographic areas.

Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke.

We used stored plasma samples from 409 patients in the National Institute of Neurological Diseases and Stroke (NINDS) tissue plasminogen activator (t-PA) Stroke Trial to examine the relationship between an apolipoprotein (Apo) E2 or an Apo E4 phenotype and a favorable outcome 3 months after stroke, the risk of intracerebral hemorrhage, and the response to intravenous t-PA therapy. For the 27 patients with an Apo E2 phenotype who were treated with t-PA, the odds ratio (OR) of a favorable outcome at 3 months was 6.4 [95% confidence interval (CI) 2.7-15.3%] compared to the 161 patients without an Apo E2 phenotype who were treated with placebo. The 190 patients treated with t-PA who did not have an Apo E2 phenotype also had a greater, though less pronounced, likelihood of a favorable outcome (OR 2.0, 95% CI 1.2-3.2%) than patients without an Apo E2 phenotype treated with placebo. For the 31 patients with an Apo E2 phenotype treated with placebo, the OR of a favorable 3 month outcome was 0.8 (95% CI 0.4-1.7%) compared to the 161 patients without an Apo E2 phenotype treated with placebo. This interaction between treatment and Apo E2 status persisted after adjustment for baseline variables previously associated with 3 month outcome, for differences in the baseline variables in the two treatment groups and in the Apo E2-positive and -negative groups, and for a previously reported time-to-treatment x treatment interaction (p = 0.03). Apo E4 phenotype, present in 111 (27%) of the 409 patients, was not related to a favorable 3 month outcome, response to t-PA, 3 month mortality, or risk of intracerebral hemorrhage. We conclude that the efficacy of intravenous t-PA in patients with acute ischemic stroke may be enhanced in patients who have an Apo E2 phenotype, whereas the Apo E2 phenotype alone is not associated with a detectable benefit on stroke outcome at 3 months in patients not given t-PA. In contrast to prior studies of head injury and stroke, we could not detect a relationship between Apo E4 phenotype and clinical outcome.

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

BACKGROUND AND PURPOSE: The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. METHODS: The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. RESULTS: There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). CONCLUSIONS: The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.